Muscular Dystrophie Emery-Dreifuss, Type LGMD1B, EDMD2 - LMNA

Clinical Features

Limb girdle muscular dystrophy type 1B (LGMD1B) is characterized by symmetrical weakness in the rump and leg musculature. Symptoms normally begin prior to 20 years of age; half of all cases begin in childhood. In a patient's 3rd and 4th decade the arms are increasingly affected; the weakness increase slowly as the disease progresses. Contractures sometimes occur in later stages.
The LGMD1B phenotype differentiates itself from the autosomal dominant Emery-Dreyfuss muscular dystrophy (EDMD1) in that it lacks significant contractures (neck, elbows, and Achilles tendons), predominant proximal limb weakness, and calf muscle hypertrophy.
Almost two-thirds of patients suffer heart disorders (e.g., dilated cardiomyopathy and cardiac irregularities), which makes cardiac treatment necessary and may require the implantation of a pacemaker. General muscle weakness usual occurs prior to the development of heart problems.
"Rigid spine", stiffness of the back and neck, and scoliosis beginning in childhood have also been observed. These should be differentiated from Rigid Spine Muscular Dystrophy (RSMD1). RSMD1 (SEPN1 gene; 1p36.13) follows an autosomal recessive pattern of inheritance is not accompanied by cardiomyopathy.
Mutations in the LMNA gene may also lead to inherited heart muscle (dilative cardiomyopathy, type 1A) or to autosomal dominant inherited Emery-Dreyfuss muscular dystrophy (EDMD2, Hauptmann-Tannhäuser type).
Classic Emery-Dreyfuss muscular dystrophy is an X-chromosomal recessive disorder caused by mutations in the Emerine gene (EMD gene, Xq28). Approximately 29% of patients show a mutation in this gene; 45% can be attributed to mutations in the LMNA gene.
In cases of verified X-chromosomal inheritance, more than 99% of patients reveal a mutation in the EMD gene; 45% of autosomal dominant EDMD2 can be attributed to mutations in the LMNA gene.

Genetic Information

LGMD1B is an autosomal dominant inherited disease. The LMNA gene, located on chromosome 1 (1q21.2), codes for a structure protein in the nucleus membrane (LMNA).